ClinVar Miner

Submissions for variant NM_001378609.3(OTOGL):c.975del (p.Leu325fs)

gnomAD frequency: 0.00005  dbSNP: rs766753922
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000219678 SCV000271430 pathogenic Rare genetic deafness 2019-09-13 criteria provided, single submitter clinical testing The p.Leu316fs variant in OTOGL has been previously reported in two individuals with hearing loss by our laboratory who were compound heterozygous for a second pathogenic variant in OTOGL. This variant has been identified in 0.08% (9/10260) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 316 and leads to a premature termination codon 6 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the OTOGL gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PVS1, PM3_Strong.
Fulgent Genetics, Fulgent Genetics RCV002500704 SCV002809685 pathogenic Autosomal recessive nonsyndromic hearing loss 84B 2021-07-03 criteria provided, single submitter clinical testing
GeneDx RCV003238740 SCV003936377 likely pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34733312, 31980526)
Center for Computational Biology & Bioinformatics, University of California, San Diego RCV004567497 SCV005049940 uncertain significance Meniere disease 2024-06-03 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.